P972: INDIRECT COMPARISON OF TECLISTIMAB IN MAJESTEC-1 VERSUS PHYSICIAN’S CHOICE OF THERAPY IN LONG-TERM FOLLOW-UP OF TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA IN DARATUMUMAB TRIALS
Authors: K. Weisel, A. Chari, S. Z. Usmani, H. Goldschmidt, M.-V. Mateos, K. Qi, A. Londhe, S. Nair, X. Lin, L. Pei, E. Ammann, R. Kobos, J. Smit, T. Parekh, M. Slavcev, P. Moreau
Journal: HemaSphere (2022)

Background: Teclistamab (tec), a B-cell maturation antigen × CD3 bispecific antibody, is currently being investigated in MajesTEC-1, a phase 1/2, single-arm trial (NCT04557098) in patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) who had received ≥3 prior lines of therapy (LOT) and previously exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Currently, there are no head-to-head trials comparing the efficacy of tec versus physician’s choice of therapy. Aims: To evaluate the comparative efficacy of tec versus physician’s choice of therapy. Methods: Patients in the long-term follow-up of 4 clinical trials of daratumumab (CASTOR, POLLUX, EQUULEUS, and APOLLO) who met the eligibility criteria for MajesTEC-1 were used to create an external control arm for MajesTEC-1. After discontinuation of trial treatments, patients (N=427) subsequently received physician’s choice of therapy, with disease progression and best treatment response assessed by the investigator. The MajesTEC-1 cohort included individual patient-level data from patients who received tec (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting with average treatment effect on the treated population was used to adjust for imbalances in baseline covariates of prognostic significance such as International Staging System stage, number of prior LOT, extramedullary plasmacytoma, time since diagnosis, age, hemoglobin, cytogenetic risk, refractory status and progression on last LOT. Efficacy assessments included overall response rate (ORR), rate of complete response or better (≥CR), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were assessed. For binary endpoints (ORR, ≥CR rate, ≥VGPR rate), odds ratio (OR) along with 95% confidence interval (CI) derived from a weighted logistic regression analysis was used to estimate the relative effect of tec vs physician’s choice of therapy. Hazard ratios (HRs) and 95% CIs were computed using a weighted Cox proportional hazards model for time-to-event endpoints (PFS, OS, and TTNT). Multiple sensitivity analyses were also conducted. Results: Baseline characteristics were comparable between the 2 cohorts after applying inverse probability of treatment weighting. Patients treated with tec had improved outcomes vs physician’s choice of therapy: ORR (OR 4.58; 95% CI 2.83–7.53; P <0.0001); ≥CR rate (OR 12.62; 95% CI 5.20–38.55; P<0.0001); ≥VGPR rate (OR 11.64; 95% CI 6.49–21.98; P<0.0001); PFS (HR 0.62; 95%CI 0.45–0.84; P=0.0024); TTNT (HR 0.38; 95% CI 0.27–0.52; P<0.0001); and OS (HR 0.47; 95% CI 0.32–0.69; P=0.0001). All sensitivity analyses showed similar results. Summary/Conclusion: In the present analysis, improved efficacy in all clinical outcomes was observed with tec versus physician’s choice of therapy, highlighting the therapeutic potential of tec to address unmet needs in patients with TCE RRMM who received ≥3 prior LOT.